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Review
. 2021 Apr 7;16(4):620-630.
doi: 10.2215/CJN.14481119. Epub 2020 Apr 1.

Inherited Tubulopathies of the Kidney: Insights from Genetics

Mallory L Downie  1   2 , Sergio C Lopez Garcia  1   2 , Robert Kleta  1   2 , Detlef Bockenhauer  1   2
Affiliations
Review

Inherited Tubulopathies of the Kidney: Insights from Genetics

Mallory L Downie et al. Clin J Am Soc Nephrol. .

Erratum in

Abstract

The kidney tubules provide homeostasis by maintaining the external milieu that is critical for proper cellular function. Without homeostasis, there would be no heartbeat, no muscle movement, no thought, sensation, or emotion. The task is achieved by an orchestra of proteins, directly or indirectly involved in the tubular transport of water and solutes. Inherited tubulopathies are characterized by impaired function of one or more of these specific transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific solutes in blood or urine to serious and life-threatening disorders of homeostasis. In this review, we focus on genetic aspects of the tubulopathies and how genetic investigations and kidney physiology have crossfertilized each other and facilitated the identification of these disorders and their molecular basis. In turn, clinical investigations of genetically defined patients have shaped our understanding of kidney physiology.

Keywords: Bartter-s syndrome; Emotions; Genomics; Homeostasis; Kidney; Kidney Tubules; Sensation; Series; Urinary Tract Physiological Phenomena; Water; kidney; kidney tubule; magnesium wasting disorders; nephrogenic diabetes insipidus; renal tubular acidosis; tubulopathies.

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Figures

Figure 1.
Figure 1.
Inherited tubulopathies are caused by dysfunction of specific transport molecules in the renal tubule. Shown is an overview of a nephron, detailing selected transporters involved in disorders of tubular sodium handling. For associated disorders, see Table 1.
Figure 2.
Figure 2.
Disorders of water are caused by impaired regulation of water reabsorption in the collecting duct. Shown is a schematic of a principal cell in the collecting duct (CD), with relevance to water transport. Note the expression of AVPR2 on the basolateral side. Activation of this receptor results in insertion of AQP2 into the apical membrane.
Figure 3.
Figure 3.
Disorders of acid-base homeostasis are caused by impaired bicarbonate reabsorption in the proximal tubule or impaired acid secretion in the collecting duct. Shown is a schematic of a tubular epithelial cell in the proximal tubule (PT) and an intercalated cell (type A) in the collecting duct (CD), highlighting proteins involved in bicarbonate reabsorption and acid secretion. For associated disorders, see Table 1.
Figure 4.
Figure 4.
Disorders of magnesium homeostasis are caused by impaired magnesium transport in TAL or DCT. Shown is a schematic of a tubular epithelial cell in thick ascending limb of the loop of Henle (TAL) and distal convoluted tubule (DCT), highlighting proteins involved in tubular magnesium handling. For associated disorders, see Table 1.
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